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Long-term hepatitis B infection in a scalable hepatic co-culture system

Author

Listed:
  • Benjamin Y. Winer

    (Princeton University)

  • Tiffany S. Huang

    (Princeton University)

  • Eitan Pludwinski

    (Hurel® Corporation)

  • Brigitte Heller

    (Princeton University)

  • Felix Wojcik

    (Princeton University)

  • Gabriel E. Lipkowitz

    (Princeton University)

  • Amit Parekh

    (Hurel® Corporation)

  • Cheul Cho

    (Hurel® Corporation)

  • Anil Shrirao

    (Hurel® Corporation)

  • Tom W. Muir

    (Princeton University)

  • Eric Novik

    (Hurel® Corporation)

  • Alexander Ploss

    (Princeton University)

Abstract

Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.

Suggested Citation

  • Benjamin Y. Winer & Tiffany S. Huang & Eitan Pludwinski & Brigitte Heller & Felix Wojcik & Gabriel E. Lipkowitz & Amit Parekh & Cheul Cho & Anil Shrirao & Tom W. Muir & Eric Novik & Alexander Ploss, 2017. "Long-term hepatitis B infection in a scalable hepatic co-culture system," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00200-8
    DOI: 10.1038/s41467-017-00200-8
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    Cited by:

    1. Yongzhen Liu & Thomas R. Cafiero & Debby Park & Abhishek Biswas & Benjamin Y. Winer & Cheul H. Cho & Yaron Bram & Vasuretha Chandar & Aoife K. O’ Connell & Hans P. Gertje & Nicholas Crossland & Robert, 2023. "Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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